ArticlePLoS genetics2012
The histone demethylase Jhdm1a regulates hepatic gluconeogenesis.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- Interactions with polygenic background impact quantitative traits in the UK Biobank.medRxiv : the preprint server for health sciences · 2025Article
- Roles of Lysine Methylation in Glucose and Lipid Metabolism: Functions, Regulatory Mechanisms, and Therapeutic Implications.Biomolecules · 2024Review
- MicroRNA-721 regulates gluconeogenesis via KDM2A-mediated epigenetic modulation in diet-induced insulin resistance in C57BL/6J mice.Biological research · 2024Article
- Histone methylation: at the crossroad between circadian rhythms in transcription and metabolism.Frontiers in genetics · 2024Review
- KDM2A Deficiency in the Liver Promotes Abnormal Liver Function and Potential Liver Damage.Biomolecules · 2023Article
- Dietary Succinate Impacts the Nutritional Metabolism, Protein Succinylation and Gut Microbiota of Zebrafish.Frontiers in nutrition · 2022Article
- Histone demethylase KDM2A: Biological functions and clinical values (Review).Experimental and therapeutic medicine · 2021Review
- Combined expression levels of KDM2A and KDM2B correlate with nucleolar size and prognosis in primary breast carcinomas.Histology and histopathology · 2020Article
- Unraveling the Regulation of Hepatic Gluconeogenesis.Frontiers in endocrinology · 2018Review
- The Landscape of Histone Modifications in a High-Fat Diet-Induced Obese (DIO) Mouse Model.Molecular & cellular proteomics : MCP · 2017Article
- Remodelling of the hepatic epigenetic landscape of glucose-intolerant rainbow trout (Oncorhynchus mykiss) by nutritional status and dietary carbohydrates.Scientific reports · 2016Article
- Article
- Transcriptional and Chromatin Regulation during Fasting - The Genomic Era.Trends in endocrinology and metabolism: TEM · 2015Review
- Article
- The epigenome and its role in diabetes.Current diabetes reports · 2012Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Hepatic gluconeogenesis is required for maintaining blood glucose homeostasis; yet, in diabetes mellitus, this process is unrestrained and is a major contributor to fasting hyperglycemia. To date, the impacts of chromatin modifying enzymes and chromatin landscape on gluconeogenesis are poorly understood. Through catalyzing the removal of methyl groups from specific lysine residues in the histone tail, histone demethylases modulate chromatin structure and, hence, gene expression. Here we perform an RNA interference screen against the known histone demethylases and identify a histone H3 lysine 36 (H3K36) demethylase, Jhdm1a, as a key negative regulator of gluconeogenic gene expression. In vivo, silencing of Jhdm1a promotes liver glucose synthesis, while its exogenous expression reduces blood glucose level. Importantly, the regulation of gluconeogenesis by Jhdm1a requires its demethylation activity. Mechanistically, we find that Jhdm1a regulates the expression of a major gluconeogenic regulator, C/EBPα. This is achieved, at least in part, by its USF1-dependent association with the C/EBPα promoter and its subsequent demethylation of dimethylated H3K36 on the C/EBPα locus. Our work provides compelling evidence that links histone demethylation to transcriptional regulation of gluconeogenesis and has important implications for the treatment of diabetes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.